GLP-2 TZ and GLP-3 RT are the two most-asked-about metabolic research peptides, and they are closely related. Both are synthetic peptides built to act at more than one hormone receptor, both carry a fatty-acid side chain that extends their half-life, and both were developed by the same kind of pharmaceutical research program. The difference is the number of receptors: GLP-2 TZ is a dual agonist (GIP and GLP-1), while GLP-3 RT is a triple agonist that adds the glucagon receptor. This guide compares them side by side.
All compounds discussed are sold for laboratory research use only. This page summarizes published research and is not guidance for human or veterinary use.
At a glance
| GLP-2 TZ | GLP-3 RT | |
|---|---|---|
| Class | Dual agonist | Triple agonist |
| Receptors | GIP, GLP-1 | GIP, GLP-1, glucagon |
| Length | 39 amino acids | 39 amino acids |
| Molecular weight | About 4.8 kDa | About 4.7 kDa |
| Half-life extension | Fatty-acid side chain (albumin binding) | Fatty-acid side chain (albumin binding) |
| Receptor profile | Favors the GIP receptor; biased signaling at GLP-1 | Most active at GIP; GLP-1 and glucagon roughly balanced |
| First published data | 2018 | 2022 |
| Longest published trials | 72 weeks (phase 3) | 48 weeks (phase 2); phase 3 under way |
| Rogue Compounds status | Research chemical, not for human use | Research chemical, not for human use |
One family, one extra receptor
Both peptides come out of incretin research, which studies the gut hormones GLP-1 and GIP and the receptors they act on. Single-receptor GLP-1 agonists came first. GLP-2 TZ was the next step: one molecule that activates both the GLP-1 and GIP receptors. GLP-3 RT goes one step further by adding activity at the glucagon receptor.
Glucagon is best known for raising blood sugar, so adding it may seem odd. In metabolic research, though, glucagon receptor activity is also linked to higher energy expenditure and to fat metabolism in the liver. The idea behind GLP-3 RT is that the GIP and GLP-1 activity reduces food intake while the glucagon activity raises energy use, which is the combination the preclinical work in obese mice reported.
GLP-2 TZ: the dual agonist
GLP-2 TZ was first described in 2018 as a fatty-acid-modified dual GIP and GLP-1 receptor agonist with pharmacokinetics suited to once-weekly administration in clinical studies. Later pharmacology work found it is “imbalanced”: it binds the GIP receptor more strongly than the GLP-1 receptor, and at the GLP-1 receptor it favors cAMP signaling over β-arrestin recruitment. Its published human data are the most extensive of the two, including a 72-week trial of 2,539 adults in which mean weight change ranged from -15.0% to -20.9% across dose groups, versus -3.1% with placebo. For more, see the GLP-2 TZ research overview.
GLP-3 RT: the triple agonist
GLP-3 RT was first described in 2022. In cell assays it was most active at the GIP receptor, with GLP-1 and glucagon receptor activity roughly balanced against each other, and its half-life in the first human study was about six days. In a 48-week phase 2 trial of 338 adults with obesity or overweight, mean weight change ranged from -8.7% to -24.2% across dose groups, versus -2.1% with placebo. A substudy found large reductions in liver fat measured by MRI. Phase 3 trials are under way. For more, see the GLP-3 RT research overview.
Where their research overlaps
- Body weight: both have been studied for weight change in adults with obesity or overweight.
- Glycemic control: both have been studied in type 2 diabetes, measuring HbA1c and glucose against placebo and against single-receptor GLP-1 agonists.
- Receptor pharmacology: both are used to study how combining incretin receptors changes signaling compared with GLP-1 alone.
- Side effects reported in trials: for both, gastrointestinal events were the most common adverse events.
How researchers choose between them
- To study the glucagon receptor’s contribution, GLP-3 RT is the relevant compound, since GLP-2 TZ has no glucagon receptor activity.
- To study dual GIP and GLP-1 agonism on its own, GLP-2 TZ isolates those two pathways without glucagon effects.
- For liver fat and energy expenditure research, GLP-3 RT’s glucagon activity is the main reason it is studied.
- For the deepest published literature, GLP-2 TZ has more and longer human trials.
What the research does not show
There is no published head-to-head trial comparing GLP-2 TZ and GLP-3 RT. Cross-trial comparisons of weight change are unreliable because the trials enrolled different populations, ran for different lengths of time and used different dose schedules. GLP-3 RT’s phase 3 results have not yet been published in full. All published human data come from clinical trials of pharmaceutical-grade products and say nothing about research-grade material.
Verify what you’re working with
GLP-2 TZ and GLP-3 RT are both 39-residue peptides with similar molecular weights, so identity testing matters. Check that the mass spectrometry result on the certificate of analysis matches the expected mass for the compound you ordered, not just the purity figure. Our guide on how to read a peptide COA walks through it, and every batch we sell is in the COA Library.
View GLP-2 TZ on Rogue Compounds · View GLP-3 RT on Rogue Compounds
Frequently asked questions
What is the difference between GLP-2 TZ and GLP-3 RT?
GLP-2 TZ is a dual agonist at the GIP and GLP-1 receptors. GLP-3 RT is a triple agonist that acts at those two receptors plus the glucagon receptor.
Is GLP-3 RT stronger than GLP-2 TZ?
There is no head-to-head trial, so the published research cannot answer that directly. Each compound was tested in separate trials with different populations, durations and dose schedules.
Why does GLP-3 RT target the glucagon receptor?
In metabolic research, glucagon receptor activity is linked to higher energy expenditure and to liver fat metabolism. Adding it is the main design difference from dual agonists.
Which has more published research?
GLP-2 TZ. Its first data were published in 2018 and it has completed phase 3 trials of up to 72 weeks. GLP-3 RT’s first data were published in 2022 and its phase 3 program is still under way.
Are GLP-2 TZ and GLP-3 RT for human use?
No. Rogue Compounds sells both as research chemicals, not for human use. They are for laboratory research only.
References
- Coskun T, et al. Mol Metab. 2018;18:3-14. PMID 30473097
- Willard FS, et al. JCI Insight. 2020;5(17):e140532. PMID 32730231
- Jastreboff AM, et al. N Engl J Med. 2022;387:205-216. PMID 35658024
- Coskun T, et al. Cell Metab. 2022;34(9):1234-1247.e9. PMID 35985340
- Urva S, et al. Lancet. 2022;400(10366):1869-1881. PMID 36354040
- Jastreboff AM, et al. N Engl J Med. 2023;389:514-526. PMID 37366315
- Sanyal AJ, et al. Nat Med. 2024;30(7):2037-2048. PMID 38858523
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.